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Establishment of a novel anti-HIV strategy targeting membranous nanotubes

Research Project

Project/Area Number 18K19457
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 49:Pathology, infection/immunology, and related fields
Research InstitutionKumamoto University

Principal Investigator

Suzu Shinya  熊本大学, ヒトレトロウイルス学共同研究センター, 教授 (80363513)

Co-Investigator(Kenkyū-buntansha) 日吉 真照  国立感染症研究所, 血液・安全性研究部, 主任研究官 (40448519)
Project Period (FY) 2018-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Keywordsエイズ / ナノチューブ / tunneling nanotubes / HIV-1 / マクロファージ / 細胞間伝播 / HIV
Outline of Final Research Achievements

In this study, we clarified a close relationship between HIV-1 and tunneling nanotubes (TNTs). We focused on M-Sec, a cellular protein involved in TNT formation, and found that its knockdown led to a reduction in not only TNTs but also viral growth, particularly viral growth in an early infection phase. We obtained a similar result for HIV-1related virus HTLV-1. More importantly, we found that M-Sec is also critical for motility of infected cells. Thus, our current study revealed that M-Sec mediates a rapid and efficient cell-cell transmission of HIV-1 at an early phase of infection by enhancing both TNT formation and cell motility.

Academic Significance and Societal Importance of the Research Achievements

エイズウイルスHIV-1は薬剤で抑えられる様になったが、完全には排除されないため、生涯の服薬を必要とし、これに伴う薬剤耐性ウイルスが問題となっている。実際、HIV-1受容体CCR5を標的にHIV-1の細胞への侵入を阻害する薬剤で成功しており、加速するには新たな標的宿主分子の同定が重要である。本研究の成果は、M-Secをその有望な候補として見出したことであり、大きな目標であるHIV-1の根絶につながる点で重要である。同時に、TNTの関与が明らかとなってきた、他の感染症、がん細胞の浸潤など、多くの病態の理解・克服にも有用である。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (9 results)

All 2019

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (7 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Expression of IL‐34 correlates with macrophage infiltration and prognosis of diffuse large B‐cell lymphoma2019

    • Author(s)
      Noyori Osamu、Komohara Yoshihiro、Nasser Hesham、Hiyoshi Masateru、Ma Chaoya、Pan Cheng、Carreras Joaquim、Nakamura Naoya、Sato Ai、Ando Kiyoshi、Okuno Yutaka、Nosaka Kisato、Matsuoka Masao、Suzu Shinya
    • Journal Title

      Clinical & Translational Immunology

      Volume: 8 Issue: 8

    • DOI

      10.1002/cti2.1074

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Increased SLAMF7<sup>high</sup> monocytes in myelofibrosis patients harboring JAK2V617F provide a therapeutic target of elotuzumab2019

    • Author(s)
      Maekawa Takaaki, Kato Shoichiro, Kawamura Toshikuni, et al.
    • Journal Title

      Blood

      Volume: 134 Issue: 10 Pages: 814

    • DOI

      10.1182/blood.2019000051

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] Tunneling nanotubes in intercellular transmission of HIV-1 and HTLV-1: similarity and difference2019

    • Author(s)
      Shinya Suzu, Masateru Hiyoshi
    • Organizer
      20th Kumamoto AIDS Seminar
    • Related Report
      2019 Annual Research Report
  • [Presentation] Physiological macrophages with un-limited self-renewing capacity2019

    • Author(s)
      Hesham Nasser, Partho Adhikary, Amira Abdel-Daim, Osamu Noyori, Hitoshi Takizawa, Ryusho Kariya, Seiji Okada, Shinya Suzu
    • Organizer
      第81回日本血液学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] HIV-1感染者の血中のIL-6高値および炎症性単球増多におけるNefの役割2019

    • Author(s)
      Hesham Nasser、野依 修、鈴 伸也
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Establishment of a simple culture model for the role of tunneling nanotubes in inter-cellular spread of HIV-12019

    • Author(s)
      Sameh Lotfi, Osamu Noyori, Hesham Nasser, Shinya Suzu
    • Organizer
      第33回日本エイズ学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] HIV-1-related disorders progression is driven by sustained Nef-induced high plasma IL-6 and altered monocytes phenotypes in infected patients2019

    • Author(s)
      Hesham Nasser, Osamu Noyori, Shinya Suzu.
    • Organizer
      第33回日本エイズ学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Virological and hematological analyses of fibrocytes in HIV-1-infected patients2019

    • Author(s)
      Osamu Noyori, Hesham Nasser, Omnia Abdel Rahman, Shinya Suzu
    • Organizer
      第33回日本エイズ学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Establishment of a simple culture model for the role of tunneling nanotubes in inter-celular spread of HIV1-2019

    • Author(s)
      Lotfi S, Noyori O, Nasser H, Suzu S
    • Organizer
      19th Kumamoto AIDS Seminar
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-07-25   Modified: 2021-02-19  

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